COVID-19 NEWS
Heals All Wounds
Can a fetal surgeon’ s treatment for diabetic wounds reduce mortality in severe COVID-19?
Fetuses don’ t scar. That insight— and its implications for wound healing in adults— led fetal and pediatric surgeon Kenneth Liechty, MD, and his research team deep into an investigation of the inflammatory response. The result: an ingenious two-pronged treatment that could potentially apply to any disease process hinging on inflammation, including acute respiratory distress syndrome, the leading cause of death in COVID-19.
Acute respiratory distress syndrome, or ARDS, has devastating consequences. A massive inflammatory response floods the alveolar sacs with fluid. Tissues scar and fibrose. Mechanical ventilation can keep patients alive until the response subsides, but there’ s no treatment.
Mortality approaches 50 %. Even when patients survive, quality of life is significantly impacted.
“ The fetus is unique in that it’ s able to regenerate a number of organs following injury, and it heals with minimal inflammation and oxidative stress,” says Dr. Liechty.“ That’ s a key pathology feature in a lot of disease processes, including ARDS.
“ So the question was,” he continues,“ how to fetalize the adult.”
THE TWO PRONGS OF INFLAMMATION
When injury occurs, the body’ s first priority is to kill pathogens and close the wound. Immune cells crowd to the site and crank out proinflammatory proteins.
“ MicroRNA are the biggest regulators of pro-inflammatory gene expression,” says Dr. Leichty,“ so we developed a strategy to target them.”
That strategy was a microRNA known as miR146a, a regulator of immune function that’ s recently played a role in studies ranging from cancer to cystic fibrosis. It binds and neutralizes messenger RNA before it can reach the ribosome to produce proteins, interrupting the inflammatory pathway.
The problem was that it didn’ t treat the other arm of inflammation: reactive oxygen species, volatile compounds that mangle the big, fragile molecules of life. Dr. Liechty’ s team had a treatment for that, too: a nanoparticle called cerium oxide, which could bind and neutralize reactive oxygen species— but without gene regulation, the immune system would just crank out more.
The key was to combine the two.
10 | CHILDREN’ S HOSPITAL COLORADO